Genetic Variant CIMAP1B:p.Arg92His (chr22-50531608-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001014440.4(CIMAP1B):c.275G>A(p.Arg92His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000142 in 1,404,168 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 8.0e-7 ( 0 hom. )

Consequence

CIMAP1B
NM_001014440.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.382

Variant links:

Genes affected

CIMAP1B (HGNC:34388): (ciliary microtubule associated protein 1B) Predicted to be active in cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

CIMAP1B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIMAP1B	NM_001014440.4 link	c.275G>A	p.Arg92His	missense_variant	Exon 3 of 7	ENST00000329363.9	NP_001014440.2	A8MYP8-1A1L1A8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ODF3B	ENST00000329363.9 link	c.275G>A	p.Arg92His	missense_variant	Exon 3 of 7	5	NM_001014440.4	ENSP00000382804.2		A8MYP8-1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151994

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

7.99e-7

AC:

AN:

1252174

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

606734

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000274

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151994

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74226

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 23, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.275G>A (p.R92H) alteration is located in exon 3 (coding exon 2) of the ODF3B gene. This alteration results from a G to A substitution at nucleotide position 275, causing the arginine (R) at amino acid position 92 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Uncertain

0.070

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.22

T;T;T

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Benign

0.70

LIST_S2

Uncertain

0.87

D;D;.

M_CAP

Pathogenic

0.85

MetaRNN

Uncertain

0.63

D;D;D

MetaSVM

Uncertain

-0.20

MutationAssessor

Pathogenic

3.4

M;.;M

PrimateAI

Pathogenic

0.81

PROVEAN

Pathogenic

-4.9

D;D;D

REVEL

Uncertain

0.48

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;.;D

Vest4

0.45

MutPred

0.69

Loss of MoRF binding (P = 0.0181);Loss of MoRF binding (P = 0.0181);Loss of MoRF binding (P = 0.0181);

MVP

0.69

MPC

3.3

ClinPred

0.92

GERP RS

4.6

Varity_R

0.80

gMVP

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over